The project involves two problems of aging of the reproductive system. First is whether steroidal "insult" to the central nervous system during a critical period in development can cause premature aging of the hypothalamo-hypophysial-ovarian axis. The second question is whether aging of the ovary induces a susceptibility to tumor formation or are tumors formed only because of a change in the endocrine environment associated with aging in higher control centers. These problems are being studied by exposing rats to various doses of steriods (androgens and estrogens) during the first 10 days postnatally. The cyclic pattern of ovarian function in these animals will then be followed over a period of months. At various times after cyclic function ceases (aged animals) ovaries will be exposed to an environment known to rapidly induce tumors. The test system involves transplantation of ovaries into castrated male parabiotic partners of castrated males; thus the ovary can be constantly exposed to high levels of follicle stimulating and luteinizing hormone. With this system we will compare endocrine functions and progress of tumor formation in "old" ovaries which have functioned normally for long periods to that of "young" ovaries which have undergone few cycles. Immunoassays of gonadotropins, as well as steroids, will be used to evaluate functional changes in the ovaries with aging.